EFFECT OF SYNOVITIS AND CORTICOSTEROIDS ON TRANSCRIPTION OF CARTILAGEMATRIX PROTEINS

Objective-To determine whether steady-state levels of type-II procolla gen, aggrecan core protein, or fibronectin mRNA in articular chondrocy tes are altered by synovitis or administration of methylprednisolone a cetate (NIPA). Sample Population-Articular cartilage specimens collect ed from 10 ponies, 2.5 to 3.5 years old and 200 to 300 kg. Procedure-4 experimental groups were compared, using the cartilage specimens: con trol, MPA-treated, lipopolysaccharide-induced synovitis, and lipopolys accharide-induced synovitis with MPA treatment. RNA was isolated from articular cartilage and compared by northern blot analysis, using equi ne-specific cDNA probes. Results-Synovitis increased steady-state leve ls of type-ii procollagen mRNA fivefold and of aggrecan mRNA twofold. Administration of a single intra-articular injection of MPA (0.1 mg/kg of body weight) decreased type-ii procollagen transcripts in normal c artilage sixfold, without significant? effect on aggrecan or total fib ronectin mRNA values. MPA treatment of inflamed joints decreased type- ii procollagen and aggrecan mRNA to levels that were not significantly different from those in untreated control specimens. Conclusions-Arti cular chondrocytes increase type-II procollagen and aggrecan synthesis in response to synovitis. MPA alters chondrocyte function in normal a nd inflamed cartilage, suggesting that potential changes in cartilage matrix protein synthesis should be considered when evaluating the ther apeutic value of intra-articular administration of corticosteroids. Cl inical Relevance-Knowledge of how synovitis and corticosteroids (indep endently and in combination) affect synthesis of cartilage matrix prot eins is relevant to understanding pathogenesis of traumatic osteoarthr itis and improving therapeutic strategies.